This application provides funds for the Washington University Drug Abuse Research Center. The application consists of three units: Core Support; Project 1, entitled Narcotics and the Hypothalamic-Pituitary-Gonadal Axis; and Project 2, entitled Narcotic Effects on the Hypothalamus: Localization Studies. The Core Support budget contains funds for the overall administration and integration of the Center's research and training activities. In addition, funds are available to bring speakers to the Center to present their drug-related research. Finally, core support has been utilized to permit the project director and principal investigators to present their data at various scientific meetings and other Drug Abuse Research Centers. The overall goal of Project 1 is to understand the mechanisms underlying the disruptive effects of the narcotics on the hypothalamic-pituitary-gonadal axis in the male rat. Specifically, our studies are directed to an examination of the effects of chronic narcotic administration and acute drug treatment on luteinizing hormone, testosterone and the structural and functional integrity of the secondary sex organs in the male rat and human. Our ultimate goal is to arrive at an understanding of the mechanisms of action of the narcotics on the hypothalamic-pituitary-gonadal axis and to pinpoint the locus of their action within this complex neuroendocrine axis. The specific aims of Project 2 are to define the neuroanatomical locus of action of the narcotics within the hypothalamus. These studies include a detailed pharmacological, biochemical and neuroanatomical investigation of the whorls of the endoplasmic reticulum observed in the arcuate nucleus of morphine-treated animals. A further goal is to attempt to determine at a microregional level in brain, the effects of the narcotics on the hypothalamic releasing factors of several anterior pituitary hormones. A final aim of this project is to examine the role of excitatory amino acids in the expression of the narcotic withdrawal syndrome in rodents. The center represents a broadly based, interdisciplinary effort to understand the basic cellular biochemical adaptations which occur as a consequence of acute and chronic narcotic administration.